Hammerton, G., Mahedy, L., Mars, B., Harold, G. T., Thapar, A.,Zammit, S., & Collishaw, S. (2015). Association between MaternalDepression Symptoms across the First Eleven Years of Their Child'sLife and Subsequent Offspring Suicidal Ideation. PLoS ONE, 10(7),[e0131885]. https://doi.org/10.1371/journal.pone.0131885

Publisher's PDF, also known as Version of recordLicense (if available):CC BYLink to published version (if available):10.1371/journal.pone.0131885

Link to publication record in Explore Bristol ResearchPDF-document

This is the final published version of the article (version of record). It first appeared online via Public Library ofScience at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131885. Please refer to anyapplicable terms of use of the publisher.

University of Bristol - Explore Bristol ResearchGeneral rights

This document is made available in accordance with publisher policies. Please cite only thepublished version using the reference above. Full terms of use are available:http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/

RESEARCH ARTICLE

Association between Maternal DepressionSymptoms across the First Eleven Years ofTheir Child’s Life and Subsequent OffspringSuicidal IdeationGemma Hammerton1*, LiamMahedy1, Becky Mars2, Gordon T. Harold3,4, Anita Thapar1,Stanley Zammit1,2, Stephan Collishaw1

1 Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UnitedKingdom, 2 Centre for Academic Mental Health, University of Bristol, Bristol, United Kingdom, 3 Andrew andVirginia Rudd Centre for Adoption Research and Practice, School of Psychology, University of Sussex,Sussex, United Kingdom, 4 International Center for Research in Human Development, Tomsk StateUniversity, Tomsk, Tomsk Oblast, Russia

* hammertongl@cardiff.ac.uk

AbstractDepression is common, especially in women of child-bearing age; prevalence estimates for

this group range from 8% to 12%, and there is robust evidence that maternal depression is

associated with mental health problems in offspring. Suicidal behaviour is a growing con-

cern amongst young people and those exposed to maternal depression are likely to be

especially at high risk. The aim of this study was to utilise a large, prospective population

cohort to examine the relationship between depression symptom trajectories in mothers

over the first eleven years of their child’s life and subsequent adolescent suicidal ideation.

An additional aim was to test if associations were explained by maternal suicide attempt

and offspring depressive disorder. Data were utilised from a population-based birth cohort:

the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were

assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was

assessed at age 16 years. Using multiple imputation, data for 10,559 families were ana-

lysed. Using latent class growth analysis, five distinct classes of maternal depression symp-

toms were identified (minimal,mild, increasing, sub-threshold, chronic-severe). Theprevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Com-

pared to offspring of mothers withminimal symptoms, the greatest risk of suicidal ideation

was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19,

4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers

with sub-threshold, increasing andmild symptoms. These associations were not fully

accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six

percent of non-depressed offspring of mothers with chronic-severe depression symptoms

reported suicidal ideation. Risk for suicidal ideation should be considered in young people

whose mothers have a history of sustained high levels of depression symptoms, even when

the offspring themselves do not have a depression diagnosis.

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 1 / 18

OPEN ACCESS

Citation: Hammerton G, Mahedy L, Mars B, HaroldGT, Thapar A, Zammit S, et al. (2015) Associationbetween Maternal Depression Symptoms across theFirst Eleven Years of Their Child’s Life andSubsequent Offspring Suicidal Ideation. PLoS ONE10(7): e0131885. doi:10.1371/journal.pone.0131885

Editor: Klaus Ebmeier, University of Oxford, UNITEDKINGDOM

Received: April 7, 2015

Accepted: June 8, 2015

Published: July 7, 2015

Copyright: © 2015 Hammerton et al. This is an openaccess article distributed under the terms of theCreative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.

Data Availability Statement: Data used for thissubmission will be made available on request to theALSPAC executive committee ( alspac-exec@bristol.ac.uk). The ALSPAC data management plan(available here: http://www.bristol.ac.uk/alspac/researchers/data-access/) describes in detail thepolicy regarding data sharing, which is through asystem of managed open access.

Funding: This research was specifically funded by aPhD stipend from the Neuroscience and MentalHealth Interdisciplinary Research Group (NNH-IRG)at Cardiff University. SC is supported by the Waterloo

IntroductionSuicidal ideation is common in adolescence and is one of the most salient risk factors for latersuicide [1]. Therefore, understanding risk factors for suicidal ideation may be important forsuicide prevention strategies [2]. Given that a large proportion of young people with suicidalideation do not present to specialist services, even when their parents are known to services [3],it is crucial to identify those most at risk in community samples.

Evidence from existing community studies suggests that maternal depressive disorder isassociated with an increased risk of later suicidal ideation in offspring [4,5]. Using a sample of240 young adolescents and their mothers (the majority of whom had a history of a mood disor-der), Garber et al found evidence for an association between maternal history of mood disorderand offspring suicidal symptoms one year later (d’ = 0.13), when adjusting for offspring base-line suicidal symptoms. A more recent study that assessed suicidal ideation repeatedly over afour year period in a sample of college students also found evidence that maternal history ofdepressive disorder, assessed retrospectively with the student, was associated with persistentsuicidal ideation in offspring [5].

The majority of previous literature has examined links between a lifetime diagnosis ofmaternal depression and offspring suicidal ideation [4,5]. Heterogeneity in the course, timingand severity of depression that might influence risk for offspring suicidal ideation is typicallynot taken into account [6]. Given that depression can be episodic or persistent, focusing onlyon a single time point or on presence or not of a lifetime diagnosis could give a misleadingimpression of the level and duration of maternal depression symptoms that offspring areexposed to. Prospective longitudinal studies enable some aspects of this heterogeneity to becaptured by identifying patterns of maternal depression symptoms over time. This allowsseverity as well as stability or change in maternal depression symptoms over time to be consid-ered. Several studies have demonstrated the added value of using longitudinal trajectories ofmaternal depression symptoms to predict offspring psychopathology over an assessment at asingle point in time or predefined measures of severity and chronicity [6,7], but these have thusfar not considered offspring risk of suicidal ideation or behaviour.

The reasons for an association between maternal depression and offspring suicidal ideationalso remain unclear. The association could be confounded by socio-demographic risk factorsthat are known correlates of maternal depression [8] and are also related to offspring suiciderisk [9]. Alternatively, shared genetic risk factors may confound the association with variantsincreasing maternal depression being transmitted and also increasing risk of offspring suicidalideation. It is also possible that the association between maternal depression and offspring sui-cidal ideation reflects causal processes. It is possible, for example, that maternal depressionleads to offspring suicidal ideation either due to exposure to maternal suicide attempt or byincreasing risk for offspring depression [10–13]. At present, however, evidence is inconclusiveand although depression itself is familial, previous studies have found that the associationbetween maternal depression and offspring suicidal ideation is not fully explained by offspringdepression [5,11]. More information from unselected population cohorts is needed to betterunderstand the degree to which risk for suicidal ideation reflects confounding by correlatedsocio-demographic adversity and shared familial risk, or the role of maternal suicide attemptor offspring depressive disorder. Finally, few studies have examined whether patterns of inter-generational risk transmission differ by gender. The increase in prevalence of suicidal ideationseen in the transition from childhood to adolescence is more pronounced in females [2], andthere is also some evidence that familial transmission of psychopathology is stronger in parentsand children of the same sex [14].

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 2 / 18

Foundation. BM is supported by an ElizabethBlackwell Institute for Health Research InstitutionalWellcome Trust Strategic Award (grant reference:097822/Z/11/ZR). The funders had no role in studydesign, data collection and analysis, decision topublish, or preparation of the manuscript.

Competing Interests: The authors have declaredthat no competing interests exist.

The present investigation examines the association between maternal depression symptomcourse over the first eleven years of their child’s life and subsequent offspring suicidal ideationat age 16 years in a large population based birth cohort. The primary hypothesis is that varia-tion in maternal depression symptom course from pregnancy to child age 11 years will be asso-ciated with subsequent offspring suicidal ideation at age 16 years over and above potentialsocio-demographic and familial confounders, with greatest risk for offspring of mothers withsevere and chronic depression symptoms. However, it is also expected that sub-thresholdmaternal depression symptoms that persist over time will be associated with increased risk ofoffspring suicidal ideation. The secondary hypothesis is that the associations observed will beattenuated, but not completely explained through maternal suicide attempt or a diagnosis ofdepression in the offspring. Analyses will also examine whether findings are similar whenexamining risk for offspring lifetime suicide attempt and whether patterns of associations differby gender.

Methods

SampleData were utilised from a large UK birth cohort study; the ‘Avon Longitudinal Study of Parentsand Children’ (ALSPAC). The cohort was set up to examine genetic and environmental deter-minants of health and development [15]. The core enrolled sample consisted of 14,541 preg-nant women resident in the former county of Avon, United Kingdom, who had an expecteddate of delivery between 1st April 1991 and 31st December 1992. Of the 14,062 live births,13,617 were singletons and were alive at one year of age. The sample is broadly representativeof the UK population, however, mothers enrolled in ALSPAC were more likely to live inowner-occupied accommodation and have a car, more likely to be married and less likely to benon-white [16]. Parents and children have been followed up regularly since recruitment viaquestionnaire and clinic assessments. Further details on the sample characteristics and meth-odology have been described previously [15,16] and detailed information about ALSPAC canbe found on the study website (http://www.bristol.ac.uk/alspac). For information on all avail-able ALSPAC data see the fully searchable data dictionary (http://www.bris.ac.uk/alspac/researchers/data-access/data-dictionary).

Ethics statement. Written, informed consent was obtained from all mothers who enteredthe ALSPAC study and ethical approval for the study was obtained from the ALSPAC Ethicsand Law committee (IRB00003312) and the Local Research Ethics Committees. The ethicscommittee specifically approved the questionnaires and the clinic testing protocols includingthe methods of gaining consent.

Given that ALSPAC is a longitudinal study with many contact points with participants, con-sent was implied for self-completion questionnaire data when postal questionnaires werereturned. All questionnaires to participants were logged when sent, reminded and returned, aswere requests not to send further questionnaires. For data collected at the focus clinics, verbalconsent was obtained from the parents or guardians on behalf of the children and verbal assentwas obtained from the children before all measures. Verbal consent was used due to the largenumber of assessments at each half day clinic. Additionally, many assessments were repeatmeasures from earlier clinics and it was considered burdensome to ask participants to supplywritten consent for every measure. It was ensured that all participants were clear what wasinvolved with each assessment and were informed that they could withdraw at any time. Allwritten consent forms are filed securely and logged electronically.

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 3 / 18

Missing dataGiven that list-wise deletion of families can increase sample bias [17], methods were taken toincorporate as much data as possible and for the derivation of latent classes, missing data washandled using full information maximum likelihood (FIML) estimation [18]. The starting sam-ple for these analyses included mothers who had information on depression symptoms from atleast five time points since birth of child to age 11 years (N = 10,559). This was done to ensurethat some data were available for each mother across the whole time period. Of the startingsample, 8,475 offspring were sent the questionnaire at age 16 years and of these 4,588 providedcomplete data on suicide-related behaviour (43% of starting sample; 1904 males and 2684females; mean age: 16.7 years, standard deviation: 0.2 years). Finally, 3,735 offspring also hadcomplete data on other covariates of interest (see Fig 1 for more details). Those missing infor-mation on outcome or covariates differed from the starting sample on a number of demo-graphic characteristics. Mothers were younger (OR 0.92 (95% CI 0.92–0.93)) and hadincreased parity (OR 1.21 (95% CI 1.16–1.27)). They were also more likely to smoke in

Fig 1. Flow chart of retention in the ‘Avon Longitudinal Study of Parents and Children’ (ALSPAC)sample.

doi:10.1371/journal.pone.0131885.g001

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 4 / 18

pregnancy (OR 2.21 (95% CI 1.91–2.35)), come from a lower social class (OR 1.97 (95% CI1.81–2.14)) and be single (OR 1.73 (95% CI 1.56–1.93)) and offspring were more likely to bemale (OR 0.61 (95% CI 0.56–0.66)).

Main analyses were run on those with complete data (N = 3,735) and on two imputed sam-ples (N = 8,475; N = 10,559). Missing data for offspring suicide-related behaviour and depres-sive disorder, maternal suicide attempt and other covariates were imputed using multivariateimputation by chained equations [19] which assumes data are missing at random (MAR) i.e.given the observed data included in the imputation model, the missingness mechanism doesnot depend on the unobserved data [17]. As the ALSPAC sample has substantial informationon socio-demographic variables that predict missingness, missing information can be assumedto be dependent on observed data. These variables were included in the imputation model tomake the assumption of MAR as plausible as possible. The imputation model also includedother measures that have been found to be closely associated with offspring suicide-relatedbehaviour and depressive disorder (such as measures of offspring suicidal ideation and self-harm at other ages, depression diagnosis and symptoms at multiple time points and measuresof substance abuse) and all other variables included in analyses. Using binary and multinomiallogistic and linear regression models as appropriate, 80 imputed datasets were derived, eachwith 10 cycles of regression switching. Predictive mean matching was used when continuousvariables were not normally distributed. All analyses were then run on imputed datasets bycombining estimates using Rubin’s rules [17]. It has been recommended that the number ofimputed datasets exceeds 100�the maximum fraction of missing information (FMI) value. FMIvalues were found to be no larger than 0.7, therefore imputing 80 datasets is adequate [17]. Allvariables with missing data used in analyses were imputed up to the maximum sample size of10,559 (i.e. those with data on latent classes of maternal depression symptoms).

S1 Table shows demographics for those with complete data on suicide-related behaviour atage 16 years and other covariates of interest (N = 3,735) and the imputed sample (N = 10,559)in comparison to the original ALSPAC cohort that met inclusion criteria for this study(N = 13,617). As shown in S1 Table, the imputation procedure has corrected for biases presentfrom selective attrition with the imputed sample being more representative of the originalALSPAC cohort than the complete case sample. Therefore, the imputed sample of 10,559 isused for all analyses hereafter; however, sensitivity checks were performed by repeating analy-ses using alternative approaches to dealing with missing data. First, analyses were rerun onthose with complete data (N = 3,735) and second, data were only imputed up to the sample ofoffspring that were sent the questionnaire measure at age 16 years (N = 8,475).

MeasuresMaternal depression symptom trajectories. Maternal depression symptoms were

assessed at 10 time points (18 weeks gestation, 32 weeks gestation, 8 weeks postnatal, 8 monthspostnatal, 1 year 9 months, 2 years 9 months, 5 years 1 month, 6 years 1 month, 8 years 1month and 11 years 2 months) using the Edinburgh Postnatal Depression Scale (EPDS) [20].The EPDS is a self-report questionnaire used to assess symptoms of depression over the pastweek. It includes 10 items, each rated on a 4-point scale (0–3). Examples of questions include: Ihave felt sad or miserable; I have been so unhappy that I have had difficulty sleeping; I haveblamed myself unnecessarily when things went wrong. It was devised for use in the postnatalperiod but it has been validated for use during pregnancy and in early parenthood using stan-dardised psychiatric interviews [21]. A cut-off at 13 has been used to predict a clinical diagnosisof depression [22]. Mothers’ scores on the EPDS at each time point correlated moderately overtime (r = .41– .64) and internal consistencies at each time point were high (α = .85– .89).

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 5 / 18

Maternal suicide attempt. Maternal suicide attempt was assessed at 10 time points (frompregnancy to child age 11 years) using a self-report life events questionnaire [23] in which themother was asked if she had attempted suicide since the previous assessment (beginning inpregnancy). All available time points were combined to create a binary ‘yes/no’ variable. Find-ings were robust to sensitivity analyses that examined alternative approaches to combiningmaternal suicide attempt across the 10 time points (i.e. only including mothers that had com-pleted a minimum of seven assessments).

Mothers known to services. Mothers were considered to be known to services if theyreported either seeing the doctor for their depression or taking medication for depression. Bothquestions were assessed at seven time points (from birth of child to child age 9 years) using aself-report questionnaire in which the mother was asked if she had seen the doctor or ‘takenpills for depression’ since the last assessment. Two binary ‘yes/no’ variables were then createdby combining all available time points from birth of child to child age 3 years and then by com-bining all available time points from child age 3 years to 9 years. Again, findings were robust tosensitivity analyses that examined alternative approaches to combining time points.

Offspring suicide-related behaviour. Suicide-related behaviour at age 16 years wasassessed via a self-report postal questionnaire [24]. Participants were classified as having a life-time history of suicidal ideation if they responded positively to either of the following ques-tions: Have you ever found yourself wishing you were dead and away from it all?;Have you everthought of killing yourself, even if you would not really do it? Participants were then asked whenthe last time was that they felt this way. The analyses in the present investigation focus on chil-dren who reported suicidal ideation in the previous year only (78% of those who reported life-time suicidal ideation by age 16 years) to preserve the time ordering of the analysis. History ofsuicidal ideation at age 11 years was assessed using the childhood interview for borderline per-sonality disorder (CI-BPD) [25] with the question: Have you thought about killing yourself?This time point was solely used in later analyses to exclude those who had already experiencedsuicidal ideation by age 11 years to rule out the possibility of reverse causation (offspring sui-cidal ideation before age 11 years influencing maternal depression trajectories).

Secondary analyses investigated specific associations with lifetime history of suicide attemptby age 16 years. Participants were classified as having made a suicide attempt if they respondedpositively to the following question: On any of the occasions when you have hurt yourself onpurpose, have you ever seriously wanted to kill yourself? Participants were also included if theyreported ‘I wanted to die’ as a reason to explain why they hurt themselves on purpose on themost recent occasion.

Offspring DSM-IV Major Depressive Disorder (MDD). Offspring diagnosis of depres-sion was assessed using the Development andWell-Being Assessment (DAWBA) [26] parent(age 7, 10 and 13 years) and child (age 15 years) versions. The DAWBA is a semi-structuredinterview consisting of open and closed questions about child mental health symptoms andtheir impact, including sections on depressive disorder, anxiety disorders, disruptive behaviourdisorders, ADHD and eating disorders. DSM-IV diagnoses of MDD over the previous monthwere generated at each time point using a well-defined computerised algorithm that predictsthe likelihood of a clinical rater assigning each child a DSM-IV diagnosis of MDD and gener-ates diagnoses (see www.DAWBA.com for more information). A senior clinical psychiatristreviewed the diagnoses and the DAWBA responses as part of the ALSPAC data collection pro-cess [27]. The presence of a DSM-IV diagnosis of MDD at any assessment was then calculated.

Potential confounders. Potential socio-demographic and familial confounding factorsassessed in pregnancy were chosen based on evidence from previous literature [8,9,28,29] andassociations with maternal depression symptoms and offspring suicidal ideation found in thepresent sample. Maternal questionnaires completed during pregnancy were used to assess

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 6 / 18

housing tenure (owned vs. rented), marital status (married vs. single), maternal level of educa-tion (below O-level, O-level or above O-level; O-level, or ordinary level, is an academic qualifi-cation taken at the end of compulsory schooling which is now defunct in the UK and has beenreplaced with GCSE examinations), self-reported psychiatric disorder before pregnancy (yes/no; including drug addiction, alcoholism, schizophrenia, anorexia nervosa, severe depressionor any other psychiatric disorder), maternal family history of depression (0, 1 or both parents)and smoking in pregnancy (smoked tobacco in either the first three months or the last twoweeks of pregnancy).

Statistical analysesLatent class growth analysis (LCGA) [30] was used to identify qualitatively distinct patterns ofdepression symptoms in mothers over time from 18 weeks gestation to child age 11 years usingthe EPDS (as a continuous scale). In LCGA, homogenous groups of mothers are identifiedbased on specific growth parameters including each mother’s initial level and rate of change indepression symptoms. Each mother is then given a probability of belonging to each class andthese probabilities are then used to assign each mother to their most likely class. In contrast togrowth mixture modeling (GMM), LCGA assumes no within class variance on the growth fac-tors (the intercept and slope) and these are set to be zero. Given that our focus was to identifydistinct groups of mothers rather than to examine within-group variability, we used the LCGAapproach which helps with the clearer identification of classes and involves less computationalburden than allowing the within class variance to be freely estimated [31].

From previous literature [8,28,32,33,34] we expected to find between three and six classes ofmaternal depression symptoms; therefore, a series of models were fitted and theoretical andstatistical steps were taken to decide which model provided the best fit to the data. Theseincluded a number of fit statistics (including the sample size adjusted Bayesian information cri-terion (SSABIC), Lo, Mendell & Rubin likelihood ratio test (LMR-LRT) and entropy values).Using the maximum probability rule, individuals were then assigned to the class for which theyhad the highest probability of membership. This approach is justified when the posterior prob-ability scores for each trajectory group are high (above at least 0.7) indicating that there is clearseparation of classes [30].

To examine if variation in maternal depression symptom course was associated with subse-quent offspring suicidal ideation, a logistic regression analysis was performed with maternaldepression class as the exposure variable (treated as a class membership categorical variable)and past year offspring suicidal ideation at age 16 years as the outcome (model 1). In model 2,potential socio-demographic and familial confounders were adjusted for. Next maternal sui-cide attempt was included in analyses to examine if the association between maternal depres-sion class and offspring suicidal ideation is explained through maternal suicide attempt (model3). In model 4, offspring DSM-IV MDD was additionally included to examine if any associa-tion found is explained through offspring depression diagnosis. Next, analyses were rerun afterexcluding offspring who reported suicidal ideation at age 11 years to rule out the possibility ofreverse causation (offspring suicidal ideation before age 11 years influencing maternal depres-sion trajectories). Lastly, a logistic regression analysis was performed between classes of mater-nal depression symptoms (withminimal class as the reference group) and offspring lifetimesuicide attempt by age 16 years. Analyses were conducted using Stata version 13 [35] andMPlus version 7 [36].

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 7 / 18

Results

Latent classes of maternal depression symptomsBased on fit statistics, size of latent classes and parsimony, a five class model represented thebest fit to the data. Model fit statistics (SSABIC (Entropy)) from 3 to 6 classes were: 505553(0.86), 503123 (0.82), 501995 (0.80), 501003 (0.77), respectively. Lower SSABIC values reflectsuperior fit of a given model; however, a non-significant LMR-LRT for the 6 class model sug-gested that the 6 class solution did not significantly improve model fit over the 5 class solution,whereas a significant LMR-LRT for the 5 class model indicated that the 5 class model didimprove model fit over the 4 class solution. The estimated posterior probability scores for eachtrajectory group for the five class model are presented in S2 Table. Probabilities can range from0 to 1 with 1 representing perfect classification. Ideally, individuals’ probability of membershipwill approach 1 for one class with small probabilities for all other classes, indicating clear sepa-ration of classes. Average posterior probabilities for most likely latent class membership for thefive class model ranged from .78 to .92 indicating relatively unambiguous classification. Find-ings from previous literature suggested that there could be a non-linear growth pattern to thedata [7,28]; therefore a quadratic growth model was also fitted. However, as the five identifiedclasses showed the same profile (results available on request), we chose to keep the more parsi-monious model (including the linear growth parameter).

Five classes of maternal depression symptoms were identified, four showing stable levels ofsymptoms over time but differing in level of severity and one showing increasing symptoms.Fig 2 shows both the model fitted linear growth trajectories for each class and the observedpseudo-class trajectories for the five identified classes of maternal depression symptoms.Approximately 5% of the sample was identified as belonging to a class with high stable symp-toms that were consistently above the clinical cut-off of 13 on the EPDS (chronic-severe class;average predicted probability of class membership: 0.93). Nearly 18% belonged to a class withsub-threshold symptoms over time, with symptom levels that were consistently just below theclinical cut-off on the EPDS and decreased very slightly over time (sub-threshold class; pre-dicted probability: 0.87). Just under 6% belonged to a class with increasing symptoms overtime, with symptom levels that rose to the clinical cut-off by the last time point (increasingclass; predicted probability: 0.78). Just over 30% of the sample belonged to a class with stablemild symptoms over time (mild class; predicted probability: 0.81). Lastly, 40% of the samplebelonged to a class with very low levels of depression symptoms over time (minimal class; pre-dicted probability: 0.92). In all further analyses theminimal class is treated as the referencegroup unless otherwise stated.

Validation of latent classes of maternal depression symptomsTable 1 shows that the pattern of association between the classes of maternal depression symp-toms and other measures used in analyses was consistent with the pattern expected. There wasa stepped increase in prevalence for most measures with increasing severity of maternal depres-sion symptom trajectories. Compared to mothers withminimal depression symptoms, motherswith chronic-severe symptoms were more likely to make a suicide attempt, live in rentedaccommodation, be single, smoke in pregnancy, have less education, have a psychiatric disor-der before pregnancy, have a family history of depression and be known to services due todepression. Offspring of mothers with chronic-severe depression were also more likely to havea diagnosis of MDD. The pattern of association was similar for mothers withmild, increasingand sub-threshold symptoms compared to mothers withminimal symptoms with a few excep-tions. There was no evidence that mothers withmild and increasing symptoms had less

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 8 / 18

education than mothers withminimal symptoms. Additionally, there was no evidence thatmothers with increasing symptoms were more likely to be single or have a family history ofdepression compared to mothers withminimal symptoms.

Association between latent classes of maternal depression symptomsand offspring past year suicidal ideation at age 16 yearsThe number of adolescents that reported past-year suicidal ideation at the age 16 years assess-ment was 672/4,588 (15%; 174 males and 498 females). Of these, 81% reported specifically thatthey had thought about killing themselves. The number of children that reported suicidal idea-tion at age 11 years was 272/5,613 (5%; 144 males and 128 females). The overall prevalence wasvery similar in fully imputed models taking account of missing data–the estimated prevalencefor past-year suicidal ideation at age 16 years was 15% (95% CI: 14–17%; 11% of males and20% of females) and the estimated prevalence for suicidal ideation by age 11 years was 6%(95% CI: 5–6%; 6% of males and 5% of females).

Fig 3 shows an increase in prevalence of offspring suicidal ideation at age 16 years withincreasing severity of maternal depression symptom trajectories. The pattern is similar formales and females, although a higher percentage of females report suicidal ideation across all

Fig 2. Five class model of maternal depression symptomsmeasured using the Edinburgh Postnatal Depression Scale (EPDS) from 18 weeksgestation to child age 11 years. Figure shows both model fitted estimated linear growth trajectories for each class (dotted line) and the observed pseudo-class trajectories for the identified classes (solid line);N = 10,559.

doi:10.1371/journal.pone.0131885.g002

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 9 / 18

classes. There was no evidence of an interaction between gender and maternal depression classon offspring suicidal ideation (results available on request).

In order to examine whether the increase in prevalence of suicidal ideation at age 16 yearswith increasing severity of maternal depression symptoms trajectories was solely due to anincrease in prevalence of offspring depressive disorder, the pattern of findings was examined in

Table 1. Pattern of maternal suicide attempt, offspring DSM-IV Major Depressive Disorder (MDD), housing tenure, marital status, smoking in preg-nancy, maternal level of education, maternal psychiatric disorder before pregnancy, maternal family history of depression andmaternal depres-sion-related service use by classes of maternal depression symptoms.

% Minimal(n = 4,177)

Mild(n = 3,384)

Increasing(n = 583)

Sub-threshold(n = 1,863)

Chronic(n = 552)

Maternal suicide attempt 0.34 1.09*** 4.12*** 3.98*** 10.87***

Offspring DSM-IV MDD 2.14 3.06# 5.87*** 7.08*** 14.34***

Housing tenure (rented) 16.05 22.77*** 19.89* 27.45*** 37.08***

Marital status (single) 16.54 22.33*** 18.89 28.54*** 32.37***

Smoked in pregnancy 16.86 22.90*** 24.79*** 29.85*** 35.92***

Maternal education (< O-level) 24.27 25.77 23.83 31.01*** 36.76***

Maternal past psychiatric disorder 4.59 10.16*** 11.22*** 21.45*** 37.63***

Maternal family history of depression (bothparents)

1.23 2.14** 1.95 3.40*** 5.97***

Maternal service use:From birth of child to age 3years

4.689.67 14.20*** 18.14*** 30.18*** 55.66***

From child age 3 years to 9 years 20.67*** 41.98*** 39.20*** 62.84***

Imputed N = 10,559# p < .10

*p � 0.05

** p � 0.01

*** p � 0.001 with minimal class as the reference group

doi:10.1371/journal.pone.0131885.t001

Fig 3. Percentage of male and female offspring with past year suicidal ideation at age 16 years foreach of the classes of maternal depression symptoms. ImputedN = 10,559.

doi:10.1371/journal.pone.0131885.g003

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 10 / 18

non-depressed offspring. A similar pattern of results was found when the percentage of off-spring with suicidal ideation, but no previous DSM-IV diagnosis of MDD was examined [mini-mal: 11% (95% CI 10–13%); mild: 14% (95% CI 12–16%); increasing: 16% (95% CI 12–21%);sub-threshold: 18% (95% CI 15–22%); chronic-severe: 26% (95% CI 20–32%)].

Next, a logistic regression analysis was performed between classes of maternal depressionsymptoms (withminimal class as the reference group) and offspring suicidal ideation at age 16years. Table 2 shows evidence for increased risk of suicidal ideation in offspring of mothersfrom each of the depression classes in comparison to the offspring of mothers withminimalsymptoms (model 1). These associations were attenuated only marginally when adjusted forpotential confounders (model 2). Additionally, the associations were not fully explainedthrough maternal suicide attempt (model 3) or offspring DSM-IV MDD (model 4). Whenexcluding offspring who reported suicidal ideation at age 11 years, findings were similar (avail-able on request). Sensitivity checks were then performed by rerunning analyses using alterna-tive approaches to dealing with missing data. Table 3 shows associations between the classes ofmaternal depression symptoms and offspring suicidal ideation (after adjusting for potentialconfounders, maternal suicide attempt and offspring DSM-IVMDD) across the different sam-ple sizes. Results were comparable when only imputing data for those offspring that were sentthe questionnaire measure at age 16 years (N = 8,475; model 2). The pattern of findings wasalso similar when using only those with complete data on outcome and covariates, however,wider confidence intervals in complete case analysis meant that associations for themild andincreasing classes dropped below significance after adjusting for all covariates (N = 3,735;model 3). Finally, there was no evidence that offspring gender moderated any of these associa-tions (available on request).

Next, a logistic regression analysis was performed between classes of maternal depressionsymptoms (this time with chronic-severe class as the reference group) and offspring past yearsuicidal ideation at age 16 years. There was evidence for decreased risk of suicidal ideation inoffspring of mothers from each of the depression classes in comparison to the offspring of

Table 2. Logistic regression analyses showing association between each class of maternal depression symptoms in comparison to minimal class(reference group) and subsequent offspring past year suicidal ideation at age 16 years (Odds Ratios (OR) and 95%Confidence Intervals (95% CI)displayed).

OR (95% CI)

Maternal depression class Model 1 (unadjusted) Model 2 a Model 3 b Model 4 c

Minimal (N = 4177) Reference group

Mild (N = 3384) 1.31 (1.09, 1.59)** 1.23 (1.01, 1.49)* 1.22 (1.01, 1.49)* 1.22 (1.00, 1.48)*

Increasing (N = 583)Sub-threshold (N = 1863)

1.59 (1.16, 2.19)**1.85 (1.50,2.27)***

1.47 (1.06, 2.04)*1.60(1.29, 1.99)***

1.43 (1.02, 1.99)*1.57(1.26, 1.95)***

1.37 (.97, 1.92) #1.51(1.21, 1.88)***

Chronic-severe (N = 552) 3.04 (2.19, 4.21)*** 2.38 (1.68, 3.37)*** 2.23 (1.57, 3.19)*** 2.01 (1.40, 2.87)***

Imputed N = 10,559# p < .10

*p � 0.05

** p � 0.01

*** p � 0.001a Adjusting for confounders assessed in pregnancy (housing tenure, marital status, maternal level of education, smoking in pregnancy, maternal family

history of depression and maternal psychiatric disorder before pregnancy)b Additionally adjusting for maternal suicide attempt (from pregnancy to child age 11 years)c Additionally adjusting for DSM-IV diagnosis of MDD in offspring (assessed using the DAWBA at ages 7, 10, 13 and 15 years)

doi:10.1371/journal.pone.0131885.t002

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 11 / 18

mothers with chronic-severe symptoms [minimal: OR 0.33 (95% CI 0.24–0.46);mild: OR 0.43(95% CI 0.31–0.60); increasing: OR 0.52 (95% CI 0.34–0.81); sub-threshold: OR 0.61 (95% CI0.43–0.86)].

Association between latent classes of maternal depression symptomsand offspring lifetime suicide attempt by age 16 yearsThe number of adolescents that reported lifetime suicide attempt at the age 16 years assessmentwas 302/4,588 (7%; 61 males and 241 females). The overall prevalence was similar in fullyimputed models taking account of missing data– 8% (95% CI: 7–9%; 5% of males and 11% offemales). S3 Table shows evidence for increased risk for suicide attempt in offspring of motherswithmild, sub-threshold and chronic-severe symptoms in comparison to the offspring of moth-ers withminimal symptoms after adjusting for potential confounders, maternal suicide attemptand offspring DSM-IV MDD.

DiscussionIn this population sample, five distinct classes of maternal depression symptoms were identi-fied. Four classes showed stable levels of depression symptoms but differed in the level of sever-ity and one class showed a change in severity, with increasing levels of depression symptomsover time. Variation in maternal depression symptom course was associated with subsequentoffspring suicidal ideation at age 16 years, with greatest risk of suicidal ideation for offspring ofmothers with chronic-severe depression symptoms. However, there were also smaller increasesin risk for offspring of mothers with sub-threshold, increasing andmild symptoms in compari-son to offspring of mothers withminimal symptoms. This is an important finding becausemore than half of this population cohort of teenagers had experienced maternal depression atthese levels. Associations between maternal depression and offspring suicidal ideation were notcompletely explained through maternal suicide attempt or a diagnosis of depression in the

Table 3. Logistic regression analyses showing association between each class of maternal depression symptoms in comparison to minimal class(reference group) and subsequent offspring past year suicidal ideation at age 16 years using alternative approaches to dealing with missing data(Odds Ratios (OR) and 95%Confidence Intervals (95%CI) displayed).

OR (95% CI) a

Maternal depressionclass

Model 1 (using full imputed data;N = 10,559) b

Model 2 (imputing those that were sent Q;N = 8,475) c

Model 3 (complete cases;N = 3,735) d

Minimal Reference group

Mild 1.22 (1.00, 1.48)* 1.22 (.98, 1.50) # 1.17 (.93, 1.47)

Increasing Sub-threshold

1.37 (.97, 1.92) #1.51 (1.21, 1.88)*** 1.38 (.96, 1.97) #1.50 (1.19, 1.90)*** 1.27 (.84, 1.90)1.58 (1.20,2.09)***

Chronic-severe 2.01 (1.40, 2.87)*** 2.08 (1.43, 3.02)*** 2.03 (1.31, 3.15)**

# p < .10

*p � 0.05

** p � 0.01

*** p � 0.001a All models adjusted for confounders assessed in pregnancy, maternal suicide attempt and DSM-IV diagnosis of MDD in offspringb Model 1 shows the fully adjusted results using the full imputed datasetc Model 2 shows the fully adjusted results using imputed data for those offspring that were sent the questionnaire at age 16 yearsd Model 3 shows the fully adjusted results using only those with complete data on all variables in analysis

doi:10.1371/journal.pone.0131885.t003

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 12 / 18

offspring. Results were similar when examining associations with offspring lifetime suicideattempt.

This is one of the first studies to examine whether there is an association between variationin maternal depression symptom course over time and subsequent offspring suicidal ideation.The results extend the findings of previous longitudinal studies that have found an associationbetween maternal depressive disorder and offspring suicidal ideation [4,5] by examining thecourse of maternal depression symptoms across a long time span and so taking account of theheterogeneity in the course, timing and severity of maternal depression. The identified trajecto-ries also extend the majority of wider research on the course of maternal depression in the gen-eral population in terms of the time scale and number of assessments used. Other population-based samples that have examined trajectories of maternal depression symptoms across shortertime spans, or fewer assessments in relation to other outcomes in offspring have also identifieda small class of mothers with chronic and severe depression symptoms and a number of morecommon classes of mothers with stable symptoms across time that differ in level of severity[7,8,28,29,32,37]. A trajectory-based approach is useful for longitudinal cohort data whererepeated assessments of mental health symptoms are available [6]. The approach means thatsymptom levels across time rather than a single time point can be used and therefore providesa more robust measure of depression as measurement error is accounted for when deriving tra-jectories. Additionally, the classes that have emerged in the mothers were meaningful in thatthey discriminated a group of offspring at high risk of developing suicide-related behaviour.

In this study, although maternal depression trajectories were mostly stable, one group ofmothers did exhibit meaningful change in symptom levels over time. Fewer studies have identi-fied a group of mothers with increasing symptoms over time [8,28,29,37] and it could be thatthis group is more likely to emerge with a longer time span of assessment [28]. Additionally,the classes that emerged in the current study support findings from two recent studies thatexamined trajectories of maternal depression symptoms (also assessed using the EPDS) frompregnancy to approximately child age 6 years [29,37]. Both studies, one using a communitysample of mothers in Brazil [29] and the other of mothers in France [37], identified a group ofmothers whose depression symptoms began to rise in the child’s preschool period, with the off-spring of these mothers being at similar risk for later psychiatric disorder as the offspring ofmothers with depression symptoms that started high and decreased over the study [29]. In thecurrent study, offspring of mothers with increasing symptoms were nearly two times morelikely to have suicidal ideation at age 16 years compared to offspring of mothers withminimalsymptoms. It should be noted however, that not only did mothers with increasing symptomshave the most uncertainty in group membership in the derivation of classes, but also, widerconfidence intervals meant there was more uncertainty in the association with offspring sui-cidal ideation, especially when using only those with complete data. In addition, there was onlyweak evidence for increased risk of suicide attempt in offspring of mothers with increasingsymptoms after adjusting for potential confounders.

Previous studies have provided strong evidence that both a diagnosis of depression [38,39]and maternal suicide attempt [40,41] increase suicide risk in adolescents. In this study, associa-tions between differing levels of maternal depression and later offspring suicidal ideation wereslightly attenuated when including maternal suicide attempt and offspring depression diagno-sis in the analysis, especially for the chronic-severe class. However, there was still evidence foran association between the classes of maternal depression symptoms and offspring suicidal ide-ation after accounting for these potential mediators. These findings extend results from studiesthat have found a retrospective diagnosis of maternal depression and maternal suicide attempthave independent links with offspring suicidal ideation and behaviour [11]. Furthermore, theseresults provide support for the view that maternal depression, in addition to contributing to

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 13 / 18

risk for a diagnosis of depression in the offspring, may also contribute to risk for suicidal idea-tion through other routes [5,11]. In our study, offspring of mothers with chronic-severe depres-sion symptoms were at highest risk of suicidal ideation with these offspring being over twotimes more likely to have suicidal ideation at age 16 years compared to offspring of motherswithminimal symptoms. In addition, there was evidence that offspring of mothers withchronic-severe symptoms were also at increased risk of suicidal ideation when compared to off-spring of mothers with sub-threshold, increasing andmild symptoms. This is unsurprising asnot only are chronic and severe symptoms of depression likely to indicate higher genetic risk,but also offspring exposed to chronic symptoms are more likely to be exposed to a variety ofenvironmental risk factors such as a negative family environment [42]. Genetic confoundingwas not something that we were able to account for in this study, however it is an importantconsideration given evidence that longitudinal stability in depression symptoms is mainlyattributable to genetic factors [43]. In this study, there was no evidence that gender moderatedany of the associations. These findings support previous studies that have found no evidence ofgender differences when examining the association between maternal suicide attempt and off-spring suicidal ideation [41], although, the findings are in contrast to evidence that the associa-tion between mother and child depression symptoms is stronger for girls compared to boys[14]. However, given that adolescent boys were more likely to drop out of the study; this mayhave affected our ability to detect gender differences.

Our findings need to be considered in the light of some additional limitations. Firstly, aswith most cohort studies, there was selective attrition over time; however, potential bias arisingfrom missing data was dealt with using multiple imputation, utilising a large amount of addi-tional information to make the assumption of missing-at-random plausible [17]. Previousstudies have recommended using multiple imputation to deal with potential bias arising frommissing data, especially when data are thought to be missing at random (conditional on theother variables included in the model) [44]. Additionally, analyses were repeated using onlythose with complete data and the pattern of findings was the same except for weaker evidenceof an association for the increasing andmild classes after adjusting for all covariates. This pat-tern of findings across imputed and complete case samples has been shown previously in stud-ies using the same sample that have reported that the association between maternal andoffspring depression may be underestimated in complete case analyses [45]. It is also importantto note that approximately 3000 families were excluded from the study initially due to substan-tial missing data on maternal depression symptoms and other measures in analyses. Those par-ticipants excluded from the study had higher levels of socio-demographic risk factors thanthose that remained in, meaning that even the associations observed in the fully imputed sam-ple may reflect conservative estimates. However, these mothers were excluded to ensure thatsome data were available on depression symptoms for each mother across the whole childhoodperiod. Additionally, S1 Table showed that the imputed sample of 10,559 was representative ofthe original ALSPAC cohort. Second, it is important to consider the possibility of reverse cau-sation i.e. offspring suicidal ideation having an adverse effect on maternal depression symptomcourse. Even though offspring suicidal ideation was assessed approximately five years after thematernal depression trajectories, some offspring may already have experienced suicidal idea-tion at earlier time points. However, when excluding offspring that reported suicidal ideationat age 11 years, conclusions remained unchanged suggesting that reverse causation is unlikelyto explain the associations observed. Third, the importance of offspring depression as a media-tor of intergenerational links may be underestimated. Although the presence of offspringDSM-IV MDD was assessed repeatedly from age 7 to age 15 years findings may not accountfor offspring that had an episode of depression between assessments or at age 16 years whensuicidal ideation was assessed. It is also possible that concurrent sub-threshold symptoms of

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 14 / 18

offspring depression at age 16 years could further explain associations. However, diagnosticmeasures of depression were unavailable at age 16 years and broader symptom screens typicallyalso tap into a range of other related psychopathology, personality traits and cognitive pro-cesses. The overlap between suicidal ideation and depression symptoms in adolescents is diffi-cult to disentangle and is something that future research should investigate more thoroughly.Fourth, we treated the derived classes of maternal depression symptoms as observed groups inanalyses examining the association with offspring suicide-related behaviour. This approachmeans that the uncertainty in latent class membership is not taken into account and can inflatedifferences between classes that are not well separated. However, when the posterior probabil-ity scores for each trajectory group are high, as in the current study, this indicates clear separa-tion of classes and provides justification for the approach that we have taken. Therefore, it isunlikely that not taking account of the uncertainty in class membership would substantiallybias the findings. Finally, risk to offspring from paternal depression was not considered, andthis could reflect an important confounding factor for associations between maternal depres-sion and offspring suicide-related behaviour.

In summary, variation in maternal depression symptoms over time was associated with sub-sequent offspring suicidal ideation and suicide attempt, with greatest risk for offspring ofmothers with chronic-severe symptoms. However, suicide risk should be considered in off-spring, even when maternal depression symptoms are below clinical levels. Offspring of moth-ers with subclinical levels of depression symptoms are an important group to consider as theseoffspring may be less likely to be known to services as mothers may have never been diagnosedwith clinical depression. In this sample, only half of mothers with sub-threshold symptomsover time were known to services. However, as expected, it is offspring of mothers with bothchronic and severe depression symptoms that are most at risk and a priority for preventiveinterventions. Additionally, as 26% of non-depressed adolescents in this group reported sui-cidal ideation at age 16 years, this highlights the importance of enquiring about suicidal idea-tion in offspring of depressed mothers, even when offspring do not have a diagnosis ofdepression. Given that the majority of mothers from the chronic-severe class were alreadyknown to services, this would be an easily identified high risk group to target [3]. These resultsmay have implications for adult mood disorder clinics, GPs and schools. The findings highlightthe importance of GPs being aware of potential problems in children of mothers with chronicdepression, and the need for adult services to consider risks in adolescent offspring of motherswith severe and chronic depression. Identifying barriers to effective communication betweenadult and child services will be important. The results also highlight the importance of educat-ing schools in being able to identify children at high suicide risk, and knowing the appropriatecourse of action to take, given that, for some children at risk, it is possible that neither parentnor child will already be known to services. Future research is needed to replicate these findingsand to examine other potential mechanisms that may explain these associations.

Supporting InformationS1 Table. Demographics of the two main samples used in analyses and the original cohortthat met inclusion criteria.(DOCX)

S2 Table. Average posterior probability scores for most likely latent class membership(row) by latent class (column) for the five class model. Bold represents average posteriorclass probability for trajectory membership.(DOCX)

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 15 / 18

S3 Table. Logistic regression analysis showing associations between each class of maternaldepression symptoms in comparison to minimal class (reference group) and offspring life-time suicidal attempt by age 16 years (Odds Ratios (OR) and 95% Confidence Intervals(95% CI) displayed). Imputed N = 10,559.(DOCX)

AcknowledgmentsWe are extremely grateful to all the families who took part in this study, the midwives for theirhelp with recruiting them, and the whole ALSPAC team, which includes interviewers, com-puter and laboratory technicians, clerical workers, research scientists, volunteers, managers,receptionists and nurses. The UKMRC and the Wellcome Trust (Grant ref: 102215/2/13/2)and the University of Bristol provide core support for ALSPAC. This publication is the work ofthe authors and Gemma Hammerton and Dr. Stephan Collishaw will serve as guarantors forthe contents of this paper.

Author ContributionsConceived and designed the experiments: GH AT SZ SC. Performed the experiments: GH LMGTH SZ SC. Analyzed the data: GH LM BMGTH SZ SC. Wrote the paper: GH LM BM GTHAT SZ SC.

References1. Brown GK, Beck AT, Steer RA, Grisham JR. Risk factors for suicide in psychiatric outpatients: a 20-

year prospective study. J Consult Clin Psychol. 2000; 68(3):371–7. PMID: 10883553

2. Lewinsohn PM, Rohde P, Seeley JR. Adolescent suicidal ideation and attempts: Prevalence, risk fac-tors, and clinical implications. Clin Psychol Pract. 1996; 3(1):25–46.

3. Potter R, Mars B, Eyre O, Legge S, Ford T, Sellers R, et al. Missed opportunities: mental disorder inchildren of parents with depression. Br J Gen Pract. 2012; 62(600):487–93.

4. Garber J, Little S, Hilsman R, Weaver KR. Family predictors of suicidal symptoms in young adoles-cents. J Adolesc. 1998; 21(4):445–57. PMID: 9757409

5. Wilcox HC, Arria AM, Caldeira KM, Vincent KB, Pinchevsky GM, O’Grady KE. Prevalence and predic-tors of persistent suicide ideation, plans, and attempts during college. J Affect Disord. 2010; 127(1–3):287–94. doi: 10.1016/j.jad.2010.04.017 PMID: 20471691

6. Nandi A, Beard JR, Galea S. Epidemiologic heterogeneity of commonmood and anxiety disorders overthe lifecourse in the general population: a systematic review. BMC Psychiatry. 2009; 9:31. doi: 10.1186/1471-244X-9-31 PMID: 19486530

7. Cents RAM, Diamantopoulou S, Hudziak JJ, Jaddoe VWV, Hofman A, Verhulst FC, et al. Trajectoriesof maternal depressive symptoms predict child problem behaviour: the Generation R Study. PsycholMed. 2013; 43(1):13–25. doi: 10.1017/S0033291712000657 PMID: 22490169

8. Skipstein A, Janson H, Stoolmiller M, Mathiesen KS. Trajectories of maternal symptoms of anxiety anddepression. A 13-year longitudinal study of a population-based sample. BMC Public Health. 2010;10:589. doi: 10.1186/1471-2458-10-589 PMID: 20925927

9. Johnson JG, Cohen P, Gould MS, Kasen S, Brown J, Brook JS. Childhood adversities, interpersonaldifficulties, and risk for suicide attempts during late adolescence and early adulthood. Arch Gen Psychi-atry. 2002; 59(8):741–9. PMID: 12150651

10. Mittendorfer-Rutz E, Rasmussen F, Wasserman D. Familial clustering of suicidal behaviour and psy-chopathology in young suicide attempters. A register-based nested case control study. Soc PsychiatryPsychiatr Epidemiol. 2008; 43(1):28–36. PMID: 17934681

11. Gureje O, Oladeji B, Hwang I, Chiu WT, Kessler RC, Sampson NA, et al. Parental psychopathologyand the risk of suicidal behavior in their offspring: results from the World Mental Health surveys. MolPsychiatry. 2011; 16(12):1221–33. doi: 10.1038/mp.2010.111 PMID: 21079606

12. Brent DA, Perper JA, Moritz G, Liotus L, Schiveers J, Balach L, et al. Familial risk factors for adolescentsuicide: a case-control study. Acta Psychiatr Scand. 1994; 89: 52–58. PMID: 8140907

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 16 / 18

13. Bridge JA, Goldstein TR, Brent DA. Adolescent suicide and suicidal behavior. J Child Psychol Psychia-try.2006; 47(3–4):372–394. PMID: 16492264

14. Lewis G, Rice F, Harold GT, Collishaw S, Thapar A. Investigating environmental links between parentdepression and child depressive/anxiety symptoms using an assisted conception design. J Am AcadChild Adolesc Psychiatry. 2011; 50(5):451–9. doi: 10.1016/j.jaac.2011.01.015 PMID: 21515194

15. Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, et al. Cohort Profile: the “children ofthe 90s”—the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol.2013; 42(1):111–27. doi: 10.1093/ije/dys064 PMID: 22507743

16. Fraser A, Macdonald-Wallis C, Tilling K, Boyd A, Golding J, Davey Smith G, et al. Cohort Profile: theAvon Longitudinal Study of Parents and Children: ALSPACmothers cohort. Int J Epidemiol. 2013; 42(1):97–110. doi: 10.1093/ije/dys066 PMID: 22507742

17. White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance forpractice. Stat Med. 2011; 30(4):377–99. doi: 10.1002/sim.4067 PMID: 21225900

18. Enders C. Applied missing data analysis. New York: Guilford; 2010.

19. Van Buuren S, OudshoomC. MICE: Multivariate imputation by chained equations (S software for miss-ing data imputation). 2000.

20. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edin-burgh Postnatal Depression Scale. Br J Psychiatry. 1987; 150:782–6. PMID: 3651732

21. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies ofthe Edinburgh Postnatal Depression Scale. Acta Psychiatr Scand. 2001; 104(4):243–9. PMID:11722298

22. Murray L, Carothers AD. The validation of the Edinburgh Post-natal Depression Scale on a communitysample. Br J Psychiatry. 1990; 157:288–90. PMID: 2224383

23. Brown GW, Harris T. Social Origins of Depression: a Study of Psychiatric Disorder in Women. London:Tavistock Press; 1978.

24. Kidger J, Heron J, Lewis G, Evans J, Gunnell D. Adolescent self-harm and suicidal thoughts in theALSPAC cohort: a self-report survey in England. BMC Psychiatry. 2012; 12(1):69.

25. Zanarini M, Horwood J, Waylen A, Wolke D. The UK version of the childhood interview for DSM-IV bor-derline personality disorder (UK-CI-BPD). Unpublished Manuscript, University of Bristol, Department ofCommunity Medicine, Unit of Perinatal and Pediatric Epidemiology, Bristol. 2004.

26. Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The Development andWell-Being Assess-ment: description and initial validation of an integrated assessment of child and adolescent psychopa-thology. J Child Psychol Psychiatry. 2000; 41(5):645–55. PMID: 10946756

27. Goodman A, Heiervang E, Collishaw S, Goodman R. The “DAWBA bands” as an ordered-categoricalmeasure of child mental health: description and validation in British and Norwegian samples. Soc Psy-chiatry Psychiatr Epidemiol. 2011; 46(6):521–32. doi: 10.1007/s00127-010-0219-x PMID: 20376427

28. Campbell SB, Matestic P, von Stauffenberg C, Mohan R, Kirchner T. Trajectories of maternal depres-sive symptoms, maternal sensitivity, and children’s functioning at school entry. Dev Psychol. 2007; 43(5):1202–15. PMID: 17723045

29. Matijasevich A, Murray J, Cooper PJ, Anselmi L, Barros AJD, Barros FC, et al. Trajectories of maternaldepression and offspring psychopathology at 6 years: 2004 Pelotas cohort study. J Affect Disord. 2015;174:424–31. doi: 10.1016/j.jad.2014.12.012 PMID: 25553403

30. Nagin D. Group-based modelling of development. Cambridge, MA: Harvard Univeristy Press; 2005.

31. Jung T, Wickrama KAS. An Introduction to Latent Class Growth Analysis and Growth Mixture Modeling.Soc Personal Psychol Compass. 2008; 2(1):302–17.

32. Barker ED. The duration and timing of maternal depression as a moderator of the relationship betweendependent interpersonal stress, contextual risk and early child dysregulation. Psychol Med. 2013; 43(8):1587–96. doi: 10.1017/S0033291712002450 PMID: 23127350

33. Campbell SB, Morgan-Lopez AA, Cox MJ, McLoyd VC. A latent class analysis of maternal depressivesymptoms over 12 years and offspring adjustment in adolescence. J Abnorm Psychol. 2009; 118(3):479–93. doi: 10.1037/a0015923 PMID: 19685946

34. Mars B, Collishaw S, Hammerton G, Rice F, Harold GT, Smith D, et al. Longitudinal symptom course inadults with recurrent depression: Impact on impairment and risk of psychopathology in offspring. JAffect Disord. 2015; 182:32–38. doi: 10.1016/j.jad.2015.04.018 PMID: 25965693

35. StataCorp. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP; 2013.

36. Muthén LK, Muthén BO. Mplus User’s Guide. Fourth Edi. Muthén & Muthén; Los Angeles; 1998–2012.

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 17 / 18

37. Van der Waerden J, Galéra C, Saurel-Cubizolles M-J, Sutter-Dallay A-L, Melchior M. Predictors of per-sistent maternal depression trajectories in early childhood: results from the EDENmother-child cohortstudy in France. Psychol Med. 2015; 13:1–14.

38. Evans E, Hawton K, Rodham K. Factors associated with suicidal phenomena in adolescents: a system-atic review of population-based studies. Clin Psychol Rev. 2004; 24(8):957–79. PMID: 15533280

39. Nock M, Green J, Hwang I, McLaughlin KA, Sampson NA, Zaslavsky AM, et al. Prevalence, Correlates,and Treatment of Lifetime Suicidal Behavior Among Adolescents: Results From the National Comorbid-ity Survey Replication Adolescent Supplement. JAMA Psychiatry. 2013; 70(3):300–10 doi: 10.1001/2013.jamapsychiatry.55 PMID: 23303463

40. Geulayov G, Gunnell D, Holmen TL, Metcalfe C. The association of parental fatal and non-fatal suicidalbehaviour with offspring suicidal behaviour and depression: a systematic review and meta-analysis.Psychol Med. 2012; 42(8):1567–80. doi: 10.1017/S0033291711002753 PMID: 22129460

41. Geulayov G, Metcalfe C, Heron J, Kidger J, Gunnell D. Parental Suicide Attempt and Offspring Self-Harm and Suicidal Thoughts: Results From the Avon Longitudinal Study of Parents and Children(ALSPAC) Birth Cohort. J Am Acad Child Adolesc Psychiatry. 2014; 53(5):509–17. doi: 10.1016/j.jaac.2013.12.022 PMID: 24745951

42. Goodman SH, Gotlib IH. Risk for psychopathology in the children of depressed mothers: a develop-mental model for understanding mechanisms of transmission. Psychol Rev. 1999; 106(3):458–90.PMID: 10467895

43. Nivard MG, Dolan CV, Kendler KS, Kan KJ, Willemsen G, van Beijsterveldt CEM, et al. Stability insymptoms of anxiety and depression as a function of genotype and environment: a longitudinal twinstudy from ages 3 to 63 years. Psychol Med. 2014; 45(05):1039–49.

44. Moodie EEM, Delaney JAC, Lefebvre G, Platt RW. Missing Confounding Data in Marginal StructuralModels: A Comparison of Inverse Probability Weighting and Multiple Imputation. Int J Biostat. 2008; 4(1).

45. Pearson R, Evans J, Kounali D. Maternal depression during pregnancy and the postnatal period: risksand possible mechanisms for offspring depression at age 18 years. JAMA Psychiatry. 2013; 70(12):1312–9. doi: 10.1001/jamapsychiatry.2013.2163 PMID: 24108418

Maternal Depression and Offspring Suicidal Ideation

PLOS ONE | DOI:10.1371/journal.pone.0131885 July 7, 2015 18 / 18